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Postoperative drug (2\u20136 weeks) challenge resulted in reduced late Na\n                    <jats:sup>+<\/jats:sup>\n                    currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na\n                    <jats:sup>+<\/jats:sup>\n                    \/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual\u00a0voltage- and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -optical\u00a0mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD\n                    <jats:sub>80<\/jats:sub>\n                    ), Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient peak signals and durations at 80% recovery (CaTD\n                    <jats:sub>80<\/jats:sub>\n                    ), times to peak Ca\n                    <jats:sup>2+<\/jats:sup>\n                    (TTP\n                    <jats:sub>100<\/jats:sub>\n                    ) and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    decay constants (Decay\n                    <jats:sub>30\u201390<\/jats:sub>\n                    ) during regular 10-Hz stimulation, and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient alternans with shortening cycle length. Isoproterenol shortened APD\n                    <jats:sub>80<\/jats:sub>\n                    in sham-operated and TAC-only hearts, shortening CaTD\n                    <jats:sub>80<\/jats:sub>\n                    and Decay\n                    <jats:sub>30\u201390<\/jats:sub>\n                    but sparing TTP\n                    <jats:sub>100<\/jats:sub>\n                    and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient alternans in all groups. All groups showed similar APD\n                    <jats:sub>80<\/jats:sub>\n                    , and TAC-only hearts showed greater CaTD\n                    <jats:sub>80<\/jats:sub>\n                    ,\u00a0heterogeneities\u00a0following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostatic, and pro-arrhythmogenic changes in intact hearts.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-66098-7","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T07:01:55Z","timestamp":1720422115000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Empagliflozin rescues pro-arrhythmic and Ca2+ homeostatic effects of transverse aortic constriction in intact murine hearts"],"prefix":"10.1038","volume":"14","author":[{"given":"Qiang","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejun","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangchuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangpeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanpei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weichao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiu","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.-H.","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhong","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"66098_CR1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1161\/CIRCULATIONAHA.117.032038","volume":"137","author":"KW Mahaffey","year":"2018","unstructured":"Mahaffey, K. 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